Anthrax is a fatal septicemic disease caused by ingestion or inhalation of Bacillus anthracis spores. Once infection is established, mortality rates may approach 90%, making B. anthracis a weapon of choice among bioterrorists. The only anthrax vaccine licensed for use in the US is plagued with problems related to low immunogenicity and a relatively high level of adverse side effects. This Phase I proposal seeks to outline the methods by which a safe, efficacious, and cost-effective DNA vaccine may be developed for the widespread prevention of anthrax disease among the general public. Various B. anthracis toxin subunits (PA, EF, and LF) and spore surface antigens (EA1, Sap, CapA, CapB, CapC, and Dep) will be tested in conjunction with Retrovax, a proprietary vaccine technology which exponentially enhances dendritic cell antigen presentation, inducing a sustained CD4+ T cell response in addition to the CD8+ T cell and antibody responses typical of DNA vaccination. This robust CD4+ response, unique among current cell-free delivery systems, should coordinate the CD8+ T cell mediated clearing of infected macrophages presenting toxin subunit peptides on their MHC Class I molecules in the early stages of anthrax infection. Humoral responses to spore surface antigens offer the ability to clear dormant anthrax spores prior to germination. Humoral responses to toxin subunits should neutralize toxin activity from any infected macrophages, which escape early immune surveillance. [unreadable] [unreadable]